Diphenyl polyamides having a cyclohexylene moiety

ABSTRACT

Novel diphenyl and loweralkyl substituted diphenyl polyamines are useful antimicrobial agents, as well as algae inhibitors. They are especially useful because of their low toxicity, and as such are advantageously included as the active agent in surgical scrubs, antibacterial soaps, as preservatives in cosmetic preparations, and the like. They also can be used for topical treatment of dermatological conditions having a bacterial origin or implication such as Acne vulgaris.

DISCLOSURE OF THE INVENTION

This invention relates to a new class of polyamines which are useful asbroad spectrum antimicrobial agents, as well as algae inhibitors. Theyare especially useful because of a surprisingly low toxicity and areparticularly suitable for topical use including use in dermatologicaland cosmetic preparations, as well as surgical scrubs and hard surfacedisinfectants. These novel compounds have the structural formula:##STR1## where each A is alike or different and is ##STR2##

Each R is alike or different and is hydrogen or loweralkyl;

Each n is alike or different and is the integer 0 or 1;

Each R₁ is alike or different and is C₁ to C₄ alkylene; and Z is##STR3## where

R₂ is 2-hydroxy-1,3-trimethylene, or R₁ as previously defined;

R₃ is 2-hydroxy-1,3-trimethylene, or R₁ as previously defined;

R₄ is hydrogen, aminoethyl, aminopropyl, C₁ to C₄ hydroxyalkyl,aminohydroxy C₂ to C₄ alkyl, or C₂ to C₄ dihydroxyalkyl;

R₅ is hydrogen, C₁ to C₄ hydroxyalkyl or C₂ to C₄ dihydroxyalkyl,aminohydroxy C₂ to C₄ alkyl, and n is as previously defined.

The compounds of this invention are preferably prepared according to thefollowing sequence of reactions:

    ______________________________________                                         ##STR4##                                                                      ##STR5##                                                                      ##STR6##                                                                      ##STR7##                                                                     ______________________________________                                    

where A, Z and n have their previously defined meanings, HX is a mono orpolybasic organic or inorganic acid, where sufficient HX is provided toprotonate at least one amino group of phenyl polyamine compound I, toform salt I(a).

The preparation of phenyl polyamine I comprises the Schiff base reactionof the appropriate ketone IV and the appropriate amine V.

If amine V has two primary amino groups, it can either be symmetrical orunsymmetrical. An amine V, which is a symmetrical amine, e.g., where R₂and R₃ are alike, n is 0, and R₄ and R₅ are hydrogen, forms a singleSchiff base VI. This is because regardless of which terminal primaryamine group of amine V reacts with ketone IV, the same product results.However, where amine V is unsymmetrical at least two products canresult. For example, if R₄ is either aminoethyl or aminopropyl, there isobtained Schiff base VI ##STR8## as well as Schiff base VI(a) ##STR9##where A, R₁₋₆ and n are as previously defined. Note that both productsVI and VI (a) come within the scope of the definition given for Schiffbase VI. Where multiple products such as Schiff bases of formulas VI andVI(a) are produced, they can be separated, if desired, by the usual andwell known separation techniques, i.e., distillation and the like.

As an alternative to obtaining a mixture of Schiff bases VI and VI(a) orVI(b), which upon reduction give a mixture of product I the reaction canbe conducted stepwise. For example 1,4-bis-(2-aminoethyl)cyclohexane maybe converted to a Schiff base with1,5-di-(4-isopropyl)-phenyl)-3-pentanone, catalytically reduced, thenthe resulting amine selectively cyanoethylated with acrylonitrile,followed by catalytic hydrogenation to furnishN-(3-aminopropyl)-N'-[1,5-di-4-isopropylphenyl)-3-pentyl]-1,4-bis(2-aminoethyl) cyclohexane. Abis(primary amine) can be dicyanoethylated with excess acrylonitrile,catalytically reduced to the corresponding N,N'-bis-(3-aminopropyl)derivative and then converted by condensation with a ketone andreduction to the desired product. For example, dicyanoethylation of1,4-bis-(2-aminoethyl) cyclohexane followed by catalytic reductionprovides N,N'-bis-(3-aminopropyl)1,4-bis-(2-aminoethyl)cyclohexane.Condensation with1-(2,4-dimethylphenyl)-6-(3-isopropylphenyl)-3-hexanone and subsequentcatalytic hydrogenation of the -C═N bond affords N-(3-aminopropyl)-N'-{3-[1-(2,4-dimethylphenyl)-6-(3-isopropylphenyl)-3-hexylamino]propyl}-1,4-bis-(2-aminoethyl)cyclohexane.

To prepare Schiff base VI, ketone IV and amine V are dissolved in asuitable inert solvent, for example, toluene, and heated to reflux,until reaction is substantially complete. Usually 5 to 20 hours issufficient for water removal by azeotropic distillation. The solvent isthen removed under reduced pressure and the residue comprising theSchiff base VI is dissolved in an inert solvent preferably an alkanol,such as ethanol or isopropanol.

After dissolution, the Schiff base VI is catalytically or chemicallyreduced.

In catalytic reductions, hydrogen saturates an alkanol solution ofSchiff base VI using agitation in the presence of the usualhydrogenation catalysts, such as transition metals and their reducibleoxides. Especially effective catalysts are the nobel metals and theiroxides. A particularly preferred catalyst is platinum oxide. Generally,the hydrogenation reaction is carried out in a manner well known in theart. Small particles, e.g., 100-300 mesh of catalyst are admixed withthe Schiff base and excess amine in alcohol and placed in a closedsystem pressurized with from 3-5 atmospheres of hydrogen gas. Afterreaction is complete, the pressure is released and the catalystseparated from the reaction mixture by filtration. The filtratecontaining the phenyl polyamine I, is then further purified by usualtechniques. Preferably, whatever solvent may be present is removed underreduced pressure, the residue then dissolved in a water-immisciblesolvent, washed with water, followed by a further washing with asaturated aqueous inorganic salt solution. After drying, the solvent isremoved by evaporation under reduced pressure giving the phenylpolyamineI usually as an oil. The phenylpolyamine can then be redissolved inloweralkanols, mixtures of loweralkanols and water, diethylether,dioxane and then neutralized with an acid, e.g., hydrogen chloride, orneutralized directly with aqueous acids.

Acid addition salts I(a) are then isolated, if desired, byprecipitation, evaporation or other usually employed techniques.

Suitable anions X for the salt I(a) include anions derived frominorganic acids as well as those of organic acids such for example ashalide, i.e., chloride, bromide or iodide or sulfate, nitrate,bisulfate, phosphate, acetate, propionate, maleate, succinate, laurate,palmitate, oleate, stearate ascorbate, gluconate, citrate carbonate,bicarbonate, benzoate, salicylate, pamoate, phthalate, furoate,picolinate, dodecylbenzenesulfonate, laurylethersulfate, nicotinate andthe like. Generally, any anion derived from an acid is suitable andsatisfactory when the polyamine salt anion X⁻, e.g., chloride isreplaced with other anions, by well known anion exchange techniques.

Alternatively, a chemical rather than a catalytic reduction isemployedto reduce Schiff base VI to product I.

In this chemically reductive procedure, the ketone IV is reacted withthe appropriate amine as before, but the Schiff base VI dissolved in analkanol or inert ether-type solvent is reacted with a chemical reductantsuch as sodium borohydride or lithium aluminum hydride, respectively.

Although as little as an equivalent of the chemical reductant can beused successfully, more satisfactory results are obtained if at leasttwo molar excess of and preferably at least a 2.5 molar excess of thechemical reductant is employed. After any initial reaction has subsided,the reaction mixture may be heated at reflux for an hour or two, thencooled to room temperature, and afterwards concentrated under vacuum.The residue obtained is then further purified as by treatment withmineral acid or inorganic base as was described for polyamines I and thesalt may thereafter be formed as previously described.

The diphenyl ketones IV are readily prepared two alternative methods,are set forth below.

A. The Condensation of Acids -- This method involves the followingreaction scheme: ##STR10##

Acylative decarboxylation of acids VII is employed by heating the acidat elevated temperatures either with transition metals, preferably iron,transition metal oxides, alkaline earth oxides, with polyphosphoric acidor with boron trifluoride. Most suitably, acylative reaction is achievedby passage of acid vapors over catalysts such as heated thoria aerogel.

Condensation-decarboxylation of an acid is the preferred method forpreparing ketone IV when each A-(R₁).sub. n group is alike and n=1, amixture of products being obtained when several different acids arecombined in a reaction. The preferred reaction comprises admixingcarboxylic acid VII with reduced iron powder and stirring in an inertatmosphere at 195° C. to 200° C. for 1-6 hours to form an iron salt.

Preferably, the carboxylic acid VII and iron are agitated under an inertatmosphere of nitrogen for at least 2 hours at 195° C. to 200° C.

After 2 hours, the temperature is increased suitably to 290° C. to 310°C. and agitation continued for at least another three hour period, fourhours usually being sufficient. The reaction mixture is allowed to cool,and then is extracted with a suitable inert solvent such as diethyletherand filtered. The solvent extracts are concentrated under reducedpressure. The residual liquid is distilled under vacuum to isolate theketone IV.

The carboxylic acids VII employed above are prepared by various meanswell known in the art.

B. Condensation of Grignard and a Nitrile

Diphenyl alkanones can be obtained according to the following reactionscheme: ##STR11## where A or (R₁)_(n) of each reactant may be the sameor different and are as previously defined.

This general procedure utilizes the reaction of a Grignard reagnetprepared from a chloro- or bromosubstituted phenyl derivative with acyanosubstituted phenyl derivative. The resultant disubstitutediminoalkane Grignard complex is hydrolyzed with aqueous mineral acid tothe corresponding ketone.

The Grignard reagent is obtained by reaction of the halide withmagnesium metal, usually in the form of turnings or powder and may becatalyzed by very small concentrations of iodine or methyl iodide.Solvents which are useful include diethyl ether, dibutyl ether,tetrahydrofuran, dioxane and benzene. Usually, gentle warming sufficesto initiate the reaction and the halide is gradually added to themetal-solvent mixture. After complete addition the disappearance ofpractically all magnesium metal signifies the end of the reaction. Asmall excess of halide is used and moisture must be excluded; a nitrogenatmosphere is beneficial. The Grignard reagent is then added to thenitrile, which is previously dissolved in two or three times its volumeof solvent, over a period of 15 minutes to 1 hour at ambienttemperature. The reaction mixture may then be heated to reflux to insurecomplete reaction. Generally, a small excess of Grignard reagent ascompared to nitrile is employed. From 1 to 10 hours at reflux issufficient for complete conversion. The resultant imine salt ispreferably decomposed and hydrolyzed to the ketone with aqueous mineralacids such as hydrochloric, sulfuric and phosphoric. The ketones arewater-insoluble and may be extracted with water-immiscible solvents.Purification is preferably accomplished by fractional distillation underreduced pressure. It is feasible to use the crude ketone reactionmixture for the alkylation of polyamines as the Grignard reactionby-products are usually alcohols of hydrocarbons and do not react withamines. The reactant halides, if present in the crude product, should beremoved prior to the ketone-amine alkylation process.

The concentrations of Grignard reagent and nitrile may be varied overwide limits for securing good yields in the process. The halide andcyano, as well as carboxylic derivatives of phenyl compounds, e.g.,phenylacetic acid are readily available.

Once the ketone IV is obtained it can then be reacted with a suitablepolyamine V. Polyamines V which are exceptionally suitable for reactionwith ketone IV includeN,N'-bis-(3-amino-2-hydroxypropyl)-1,4-cyclohexanebis(methylamine);N-(3-aminopropyl)-1,4-cyclohexanebis(methylamine);N,N'-bis(3-aminopropyl)-1,4-bis(2-aminoethyl)-cyclohexane;N-(2-aminoethyl)-1,4-bis-(2-aminoethyl)cyclohexane;N-(2-hydroxyethyl)-1,4-cyclohexanebis(methylamine);N,N-bis-(3-hydroxypropyl)-1,4-cyclohexanebis(methylamine);N-(2,3-dihydroxypropyl)-1,4-cyclohexanebis(methylamine), andN-(3-aminopropyl)-N'-(2-hydroxyethyl)-1,4-cyclohexanebis(methylamine).

The compounds described herein are excellent broad spectrumantimicrobial agents which are especially effective against grampositive and negative bacteria, particularly troublesome gram-negativemembers of the genus Pseudomonas at aqueous concentrations of 1.0 to 100ppm. Examples of susceptible species include, inter alia, Staphylococcusaureus, Streptococcus pyogenes, Bordetella bronchiseptica,Corynebacterium acnes, Pasteurella multocida, Escherichia coli,Salmonella typhimurium, S. pullorum, Klebsiella pneumoniae, Aerobacteraerogenes, Pseudomonas aeruginosa, Desulfovibrio desulfuricans, Bacillusmycoides, fungi such as Aspergillus niger and Chaetomium globosum andyeast such as Candida albicans, as well as algae.

For use, these compounds can be applied neat or employed in a dilutedform. Satisfactory diluents include any inert material not destructiveof the antimicrobial activity and especially liquid formulationscomprising aqueous dispersions, solutions, and emulsions. Solid diluentsinclude talc, corn starch, alumina and diatomaceous earth. Theanitmicrobial agents of this invention can also be deposed on materialssuch as natural fibers including oaper, cotton, wool and syntheticfibers such as nylon, polypropylene, as well as upon inanimate surfacesincluding hard surfaces such as wood, glass, metal, tile, rubber,plastic, and porous surfaces such as concrete, leather and the like.

The polyamines of this invention are especially useful in suppressingthe growth of aerobic and anaerobic bacteria in fluids employed incutting and grinding operations, such as metal working, and oil welldrilling muds or secondary oil recovery waters and brines. Anaerobessuch as the sulfate-reducer, Desulfovibrio desulfuricans, are inhibitedat 0.1- 10 ppm. concentration of these polyamines. Suppression of thesebacteria eliminates hydrogen sulfide production and corrosion ofequipment, plugging of oil-bearing sands, malodors and other deleteriousactions. These compounds are also useful in the preservation againstbiodeterioration of other aqueous systems such as aqueous emulsions anddispersions, paints or coatings, pigment suspensions, adhesives and thelike where proliferation of microorganisms can produce colloidbreakdown, pH shifts, malodors, corrosive substances, viscosity loss andother undesirable effects.

One particularly useful application of the compounds of this inventionis imparting sanitizing properties to fabrics, either woven ornon-woven, launderable or disposable, which are to be employed, such forexample, as diapers, surgical masks, caps, gowns, towels and drapes,covers for hospital furniture or instrument wrappings, aseptic facialtissues and sanitary napkins and bathroom tissue. In this application,the compounds of Formula I can be applied to the fibrous pulp beforeextracting or strand or thread formation or it can be sprayed upon thefinished goods. Either deposition technique is satisfactory so long asfrom 1 × 10⁻⁴ % or more by weight of the antimicrobial material isretained on the cloth. Greater than 0.1% to 1% by weight is generallyexcessive and superfluous.

Another application is alone or in solution or suspension or inconjunction with soaps or detergents for use in cleansing the skin,particularly in presurgical scrubbing formulations, or in formulationsfor controlling the growth of Corynebacterium acnes. C. Acnes is astrain of bacteria implicated in acne conditions, especially Acnevulgaris. Applications of as little as 1 to 5 ppm. is effective incontrolling such skin dwelling bacteria. Larger concentrations can beused if desired without irritation or discomfort such as 2500 ppm andhigher. Where the cleansing formulation is diluted with water upon use,the formulation can comprise from 0.01% by weight and more of thepolyamine of this invention.

In addition, the compounds described herein can be employed in impoundedwater, such as swimming pools, ponds or industrially-used water such ascooling or papermill water to inhibit growth of undesirable bacteria,fungi, and/or algae.

In the control of slime-producing microorganisms and algae inrecirculating industrial waters, particularly cooling operations andespecially installations such as cooling towers, the polyamine compoundsof this invention are usually employed alone, but can also be used incombination with other antimicrobial agents. The compounds arepreferably employed as salts to enhance solubility. Concentrations inthe recirculating water of as little as 1 × 10⁻⁴ % by weight areeffective in inhibiting microbial growth. To insure effectiveness,especially against more resistant strains of microorganisms, and alsowhen make-up water is added to replace water lost by evaporation and thelike, concentrations of from 1 × 10⁻⁴ % to 5 × 10⁻² % by weight are mostsatisfactory. Dosage may be continuous or as intermittent "shocktreatment", i.e., addition in a 10-20 minute period every 4-8 hours.

An unusual, highly advantageous property of these compounds is highsubstantivity to all kinds of surfaces; this provides protection againstcorrosion and acts as a storage depot for continuously dosing the watersin contact. The same properties also are largely responsible for thepreviously stated utility as disinfectants for inanimate surfacescomprising walls and ceilings, equipment, animal pens, hospitalfacilities, kitchens and bathrooms and the like, and can be convenientlyapplied as a spray or an aerosol.

In formulating the compounds of this invention for the above uses, thesecompounds can be employed in combination with other antimicrobialagents, surfactants, insecticides, defoamers, odorants, or as chelatesof metals such as copper, calcium, magnesium and iron.

Agricultural uses for these compounds include the control of microbialdamage to plants and seeds by application to the involved surfacesareas. The compounds of this invention show high orders of bacterialinhibition and are especially useful for this purpose. Some of thediseases which are of commercial importance in decreasing yield andquality and are controlled by the compositions of the invention are fireblight of apple and pear, bacterial spot on stone fruit, cherry leafspot, walnut blight, common blight of bean, bacterial spot of tomato andpepper, and potato seed piece decay. The effective concentration ofpolyamines required varies from 5-100 parts per million; they may beapplied as dusts, powder dispersions, aqueous solutions, emulsions inwater, or as aqueous dipping baths. Other plant diseases which can becontrolled by treatment with these formulations are fungal in origin,such as the many kinds of powdery mildew and leaf scabs.

For seed treatment, proportions as low as 1 to 4 ounces per hundredweight (550 to 660 ppm on seed) are effective against various fungi.

For agricultural uses, the compounds of the invention are most suitablyused in the form of aqueous suspensions or emulsions, the free baseproducts being generally insoluble in water. For this type offormulation various powdered carriers can be employed to aid inachieving uniform distribution. Talc, fuller's earth, calcium silicate,calcium carbonate, clays and the like are admixed with the agent alongwith wetting and dispersing agents and sticking agents. For maximumchemical compatability those which are non-ionic in character arepreferred. Other anionic or cationic surfactants are also satisfactory.

Additional applications for the compounds of this invention includeinhibiting formation of dental plaque especially when used as an oralrinse, e.g., a mouth wash, or in combination with a toothpaste or toothpowder containing from 50-1,000 ppm.

The following specific examples are further illustrative of ourinvention, but should not be construed as any limitation on the compoundpresented in formula I or the appended claims.

PREPARATION A Preparation of 1,5-Di-(4-Isopropylphenyl)-3-pentanone

3-(4-Isopropylphenyl)propionic acid (0.20 mole) and iron (hydrogenreduced, 6.15 g., 0.11 mole) are heated for 1.5 hours at 195° C. under anitrogen atmosphere. After that time, the temperature is increased to290° C. and maintained at that temperature for three hours. The cooledreaction mass is extracted well with ether, filtered through Celite, andthe etheral extracts concentrated under vacuum. The residue is strippedunder vacuum to leave the product, 17.3 g. (51%).

In an analogous manner there are obtained the following ketones.

1,7-Di-(4-isopropylphenyl)-4-heptanone;

1,9-Diphenyl-5-nonanone;

1,5-Diphenyl-3-pentanone;

1,3-Diphenylacetone;

1,3-Di-(4-isopropylphenyl) acetone;

1,7-Diphenyl-4-heptanone;

1,3-Di-(4-t-butylphenyl) acetone;

1,7-Di-(4-ethylphenyl)-4-heptanone;

1,7-Di-(2-methyl-5-t-butylphenyl)-4-heptanone;

1,5-Di-(2-isopropylphenyl)-3-pentanone;

1,5-Di-(2,4,6-trimethylphenyl)-3-pentanone;

1,9-Di-(2-ethylphenyl)-5-nonanone;

1,5-Di-(4-t-bitylphenyl)-3-pentanone;

1,5-Di-(4-methylphenyl)-3-pentanone;

1,7-Di-(4-t-butylphenyl)-4-heptanone.

PREPARATION B Preparation of 4-Phenyl-1-(4-isopropylphenyl)-butanone-2

A Grignard reagent was prepared from 2-phenylethyl bromide 21 gm. (0.11mole) and magnesium, 2.4 g. (0.1 gram atom). The magnesium is coveredwith 25 ml. of anhydrous ether, a crystal of iodine added and in anitrogen atmosphere, the halide dissolved in 50 ml. of anhydrous etheris added, once initial reaction is obtained, at reflux temperature overa period of 1-2 hours. After complete addition, refluxing is continuedfor 1/2 hour.

In a nitrogen atmosphere, the Grignard solution is clarified by passagethrough a glass wool filter plug and added slowly to an agitatedsolution of 4-isopropylphenylacetonitrile, 14.9 gm. (0.09 mole) in 200ml. of anhydrous diethyl ether. A gentle reflux is maintained during theaddition which requires 1/2 to 1 hour. After complete addition and anadditional 15 minutes at reflux, the reaction mixture is cooled andpoured onto a mixture of 50 ml. of concentrated hydrochloric acid and200 gms. of ice using good mixing. Upon warming the ether is removed bydistillation and the residue heated at 70°-100° C. for 1 hour. Theproduct is extracted with two portions, 250 ml. each of ether, the ethersolution dried over anhydrous magnesium sulfate and the solvent removed.Any of the reactants, i.e., halide and nitrile, are separated from theketone by fractional distillation under reduced pressure along withby-products.

In a similar procedure, the following ketones are prepared:

1-(2-Methylphenyl)-4-phenylpentan-2-one;

1-(4-t-Butylphenyl)-5-(4-isopropylphenyl)-pentan-3-one;

2-(3-Methylphenyl)-8-(2-isopropylphenyl)-octan-4-one;

1-(3-Methylphenyl)-4-(4-n-butylphenyl)-2-pentanone;

1,4-Di-(4-isopropylphenyl)-2-butanone;

1-Phenyl-3-(4-t-butylphenyl)acetone;

1-(3,4-Dimethylphenyl)-5-(4-isopropylphenyl)-3-pentaonone;

2,6-Diphenyl-4-heptanone.

PREPARATION C Preparation ofN-(3-Aminopropyl)-1,4-cyclohexanebis-(methylamine)

Acylonitrile (26.5 g., 0.5 mole) is added dropwise over a 45 minuteperiod to 1,4-cyclohexanebis(methylamine) (2.84 g., 2.0 mole) withstirring and ice bath cooling. After complete addition, the reactionmixture is stirred an additional 1 hour at 5° C., gradually warmed to45° C. and kept 2 hours at that temperature followed by 1 hour at 90° C.The reaction mixture is stripped of any unreacted acylonitrile andexcess non-cyanoethylated bis(methylamine) starting material which wasremoved at an internal temperature of 110° C. and 1 mm. The residue isthen dissolved in 1.5 l. of ethyl alcohol (ammonia gas saturated) mixedwith 50 ml. of sponge nickel catalyst and hydrogenated at 150 psi. Afterremoval of catalyst by filtration, the solvent and ammonia is strippedoff and the triamine product purified by fractionation under reducedpressure.

A higher homolog, N-(3-aminopropyl)-1,4-cyclohexanebis-(2-ethylamine) issynthesized using the above procedure with1,4-bis-(2-aminoethyl)cyclohexane prepared according to P. P. Garcia andJ. H. Wood, J. Org. Chem., 26, 4167 (1961). Excess staring amine in thisexample may be separated from product at a boiling point of 122° C.-126°C./ 1 mm.

PREPARATION D Preparation ofN-(3-Aminopropyl)-N'-(2-hydroxyethyl)-1,4-cyclohexanebis(methylamine)

Acylonitrile (10.6 g., 0.2 mole) is added dropwise over a 15 minuteperiod to N-(2-hydroxyethyl)-1,4-cyclohexanebis(methylamine) (37.2 g.,0.4 mole) with stirring and ice bath cooling. After complete addition,the reaction mixture is stirred an additional 2 hours at 5° C., allowedto gradually warm over a 1 hour period, heated 2 hours at 45° C. It isthen fractionated under reduced pressure up to an internal temperatureof 170° C. The residue is dissolved in 200 ml. ethyl alcohol, cooled inan ice bath and saturated with ammonia gas at 0° C. Approximately 5 ml.of sponge nickel catalyst (W. R. Grace Co., Davison Chem. Division) isadded and the mixture shaken under hydrogen at 150 psi until no furtherhydrogen uptake. The catalyst is removed by suction, filtration undernitrogen, the solvent stripped away and the residue fractionallydistilled under reduced pressure. The triamine product is readilydistinguished from cyanoethylated diamine by its lower R_(f) on slicagel using a solution of 1 volume concentrated aqueous ammonium hydroxidein 4 volume methyl alcohol. The synthesis is an adaptation of the methodof M. Israel et al, J. Med. Chem., 7, 710 (1964) for the preparation ofpolymethylenepolyamines.

PREPARATION E Preparation ofN-(2-Hydroxyethyl)-1,4-cyclohexanebis(methylamine)

A solution of 14.2 gm. (0.1 mole) of 1,4-cyclohexanebis(methylamine) in150 ml. anhydrous methyl alcohol and under an atmosphere of nitrogen iswarmed to 45° C.-50° C. In a 20 minute period, there is introduced withgood agitation and beneath the liquid surface a total of 1.1 gm. (0.025mole) of ethylene oxide in gaseous form. The reaction temperature ismaintained at 45° C.-50° C. for an additional one-half hour afterstopping the addition of ethylene oxide. The methyl alcohol is removedby distillation at atmospheric pressure; excess1,4-cyclohexanebis(methylamine) is readily separated from the product byfractionation under reduced pressure. Only monoethoxylated compoundremained and could be used as such or further purified by distillationat reduced pressure.

PREPARATION F Preparation ofN-(3-Amino-2-hydroxypropyl)-1,4-cyclohexanebis(methylamine)

1,4-Cyclohexanebis(methylamine) (14.2 g., 0.1 mole) is dissolved in 50ml. of anhydrous methyl alcohol and the solution cooled to +5° C. in anice bath. Epichlorohydrin (9.3 g., 0.1 mole) is added in a 2-minuteperiod and the temperature maintained at +5° C. for 2 hours; reaction isallowed to continue at 10° C-15° C. until thin layer chromatography ofan aliquot (silica gel plate with development using a solution of 1volume concentrated aqueous ammonium hydroxide in 4 volumes of methylalcohol) indicated nearly complete conversion of the starting diamine tothe propylene chlorohydrin. The solution is then added to 100 ml. of drywith methyl alcohol previously saturated at 0° C. with dry ammonia gasby continuous dropwise flow at +5° C. with good agitation and externalcooling. After stirring 2 hours at °5° C., it is allowed to warm to 20°C. and mixed overnight. The reaction is competed by heating at 45°C.-55° C. for 6 hours. The solvent and ammonia was removed by strippingand the product purified using fractional distillation under reducedpressure.

N-(2,3-Dihydroxypropyl)-1,4-cyclohexanebis(methylamine) is produced byalkaline hydrolysis of the above propylenechlorohydrin derivative.

The propylene chlorohydrin derivative is dissolved in a 1M sodiumhydroxide solution containing 50% methyl alcohol and 50% water by weightin a ratio of 5 grams of chlorohydrin to 25 ml. of sodium hydroxidesolution. After stirring 24 hours at 20° C. the methyl alcohol isremoved by distillation and the oil which separates is extracted with100 ml. of diethyl ehter. The extract is washed with approximately 10ml. of cold water, the ether layer dried over anhydrous sodium sulphateand then filtered. Removal of the ether by distillation leaves theproduct in good purity as an oil.

PREPARATION G Preparation ofN,N'-bis-(3-Aminopropyl)-1,4-bis-(2-aminoethyl)cyclohexane

Acrylonitrile (10.6 g., 0.2 mole) is added dropwise over a 15 minuteperiod to 1,4-bis-(2-aminoethyl)-cyclohexane (17.0 g., 0.1 mole) cooledin an ice bath and with good stirring. The resultant solution ismaintained at 5° C. -10° C. with agitation for 1 hour, allowed to warmto 25° C. over a 2 hour period and finally heated at 90° C.-95° C. for 4hours. The reaction mixture is then freed of any unreacted material andmonocyanoethylated product by gradually heating to an internaltemperature of 130° C. at a pressure of 0.5-1 mm. The residue isdissolved in 200 ml. ethyl alcohol which had been previously saturatedwith dry ammonia gas at 0° C., mixed with approximately 5 ml. of asponge nickel catalyst suspension and reduced with shaking under 200 psihydrogen. The catalyst is removed by suction filtration, the filtratestripped of solvent and the residue purified by fractional distillationunder reduced pressure.

PREPARATION H Preparation ofN-(2-Aminoethyl)-1,4-bis-(2-aminoethyl)-cyclohexane

1,4-Bis(2-aminoethyl) cyclohexane (68 g,m., 0.4 mole) and ethyleneimine(4.3 gm., 0.1 mole) with 0.4 g. ammonium chloride are mixed in aglasslined pressure reactor and filled with nitrogen to 100 psi. Themixture is shaken and heated at 85° C.-95° C. for 48 hours. Aftercooling, it is distilled rapidly free of the salt and then fractionatedunder high vacuum. The starting diamine is readily distinguished fromthe triamine product by thin layer chromatography and silica gel using amixture of 1 volume concentrated aqueous ammonium hydroxide with 4volume methyl alcohol, the diamine having a much higher R_(f).

PREPARATION I N,N-Bis-(3-hydroxypropyl)-1,4-cyclohexanebis(methylamine)Preparation of 1-Cyano-4-[di-(3-hydroxypropyl)aminomethyl]-cyclohexaneand catalytic reduction

a. 1-Bromomethyl-4-cyanocyclohexane (20.2 g., 0.1 mole) anddi-(3-hydroxypropyl)amine (53.2 g., 0.4 mole) in 400 ml. of anhydrousisopropyl alcohol are heated in an autoclave at 105° C.-115° C. for 8hours with continuous agitation. The reaction mixture is stripped ofsolvent under reduced pressure and the residue diluted with 500 ml. ofice water. A cold solution of 5 g. of sodium hydroxide in 100 ml. ofwater is added and the mixture extracted with two 150 ml. portions ofmethylene chloride. The organic phase is then washed with 50 ml. of icewater, dried overnight with anhydrous sodium sulfate, filtered and freedof solvent by distillation under reduced pressure.

b. The residual oil from a.) is taken up in 200 ml. of anhydrous ethylalcohol previously saturated at 0° C. with dry ammonia gas, mixed with 5ml. of sponge nickel catalyst suspension and hydrogenated at 25° C.under 100 psi hydrogen pressure in a stirred autoclave. The reactioncompletion is readily determined by disappearance of the C.tbd.N IRabsorption band and measurement of hydrogen uptake. The catalyst isremoved by suction filtration, the solvent with mild heating underreduced pressure and the product obtained pure with fractionaldistillation at reduced pressure.

EXAMPLE 1

N,N'-bis-(3-aminopropyl)-1,4-bis-(2-aminoethyl)-cyclohexane and1,5-di(4-isopropylphenyl)-3-pentanone in 250 ml. toluene is heated atreflux overnight with a Dean-Stark water separator. The cooled solutionis concentrated under reduced pressure. The residue is dissolved inethanol and hydrogenated with 1.5 g. PtO₂ at room temperature and 40 psihydrogen pressure. The platinum catalyst is filtered off and the ethanolremoved under vacuum. The residual oil is dissolved in ether and theether solution washed several times with water to remove the excess3,3'-iminobispropylamine. The ether extracts are dried over anhydroussodium sulfate and concentrated under vacuum to leave the polyamine as acolorless oil.

The o8il is dissolved in ether and hydrogen chloride gas is bubbled intothe solution until no further precipitation occurs. The ether isevaporated under reduced pressure to leave the product as a solid whichis digested with hot isopropyl alcohol. The solids are collected byfiltration and dried under vacuum at 70° C. to give a colorless product,N-(3-aminopropyl)-N'-[3-[1,5-di-(4-isopropylphenyl)-3-pentylamino]propyl]-1,4-bis-(2-aminoethyl) cyclohexanetetrahydrochloride.

In an analogous manner from the ketones and the amines set forth below,there are prepared the following compounds of this invention.

                                      TABLE I                                     __________________________________________________________________________    Ketone             Amine            Product                                   __________________________________________________________________________    1,7-Di-(4-t-butylphenyl)-                                                                     N,N'-bis-(3-aminopropyl)-                                                                      N-(3-aminopropyl)-N'-{3-[1,7-di-(4-t-        4-heptanone     1,4-bis-(2-aminoethyl)-                                                                        butylphenyl)-4-heptylamino]propyl}-1,4-                      cyclohexane      bis-(2-aminoethyl)cyclohexane                1,7-Di-(2-methyl-5-t-                                                                         N,N'-bis-(3-aminopropyl)-                                                                      N-(3-aminopropyl)-N'-{3-[1,7-di-(2-methyl                                     -                                            butylphenyl)-4-heptanone                                                                      (2-aminoethyl) cyclohexane                                                                     5-t-butylphenyl)-4-heptylamino]propyl}-1,                                     4-                                                                            bis-(2-aminoethyl) cyclohexane               1,5-Di-(4-methylphenyl)-                                                                      N,N'-bis-(3-aminopropyl)-                                                                      N-(3-aminopropyl)-N'-{3-[1,5-di-(4-methyl                                     -                                            3-pentanone     1,4-bis-(2-aminoethyl)-                                                                        phenyl)-3-pentylamino]propyl}-1,4-bis-(2-                                     u                                                            cyclohexane      aminoethyl) cyclohexane                      1,5-Di-(2,4,6-trimethyl-                                                                      N-(2,3-dihydroxypropyl)-                                                                       N-(2,3-dihydroxypropyl)-N'-[1,5-di-(2,4,6                                     -                                            phenyl)-3-pentanone                                                                           1,4-cyclohexanebis-                                                                            trimethylphenyl-3-pentyl]-1,4-cyclohexane                                     bis-                                                         (methylamine)    (methylamine)                                1,7-Di-(4-isopropylphenyl)-                                                                   N-(2,3-dihydroxypropyl)-                                                                       N-(2,3-dihydroxypropyl)-N'-]1,7-di-(4-iso                                     -                                            4-heptanone     1,4-cyclohexanebis-                                                                            propylphenyl)-4-heptyl]-1,4-cyclohexanebi                                     s-                                                           (methylamine)    (methylamine)                                1,3-Di-(4-t-butylphenyl)-                                                                     N-(3-aminopropyl)-N'-2-                                                                        N-{3-[1,3-di-(4-t-butylphenyl)-2-propylam                                     ino]-                                        acetone         hydroxyethyl-1,4-cyclo-                                                                        propyl}-N'-(2-hydroxyethyl)-1,4-cyclohexa                                     ne-                                                          hexanebis(methylamine)                                                                         bis(methylamine)                             1,5-Di-(4-isopropylphenyl)-                                                                   N-(3-aminopropyl)-N'-2-                                                                        N-(2-hydroxyethyl)-N'-{3-[1,5-di-(4-         3-pentanone     hydroxyethyl-1,4-cyclo-                                                                        isopropylphenyl)-3-pentylamino]propyl}-                      hexanebis(methylamine)                                                                         1,4-cyclohexanebis(methylamine)              1,3-Di-(4-isopropylphenyl)-                                                                   N-(3-aminopropyl)-N'-2-                                                                        N-(2-hydroxyethyl)-N'-{3-[1,3-di-(4-         acetone         hydroxyethyl-1,4-cyclo-                                                                        isopropylphenyl)-2-propylamino]propyl}-                      hexanebis(methylamine)                                                                         1,4-cyclohexanebis(methylamine)              1,3-Di-(4-t-butylphenyl)-                                                                     N-(2,3-dihydroxypropyl)-                                                                       N-[1,3-di-(4-t-butylphenyl(-2-propyl]-N'-    acetone         1,4-cyclohexanebis-                                                                            (2,3-dihydroxypropyl)-1,4-cyclohexanebis-                    (methylamine)    (methylamine)                                1,9-Diphenyl-5-nonanone-                                                                      N-(2,3-dihydroxypropyl)-                                                                       N-(2,3-dihydroxypropyl)-N'-(1,9-diphenyl-                                     5-                                           diphenyl        1,4-cyclohexanebis-                                                                            nonyl)-1,4-cyclohexanebis(methylamine)                       (methylamine)                                                 1,5-(Diphenyl-3-pentanone                                                                     N,N'-bis-(3-aminopropyl)-                                                                      N-(3-aminopropyl)-N'-[3-(1,5-diphenyl-3-                     1,4-bis-(2-aminoethyl)-                                                                        pentylamino)propyl]-1,4-bis-(2-amino-                        cyclohexane      ethyl)cyclohexane                            Dibenzylketone  N,N'-bis-(3-aminopropyl)-                                                                      N-[3-aminopropyl)-N'-[3-(1,3-diphenyl-2-                     1,4-bis-(2-aminoethyl)-                                                                        propylamino)propyl]-1,4-bis-(2-aminoethyl                                     )-                                                           cyclohexane      cyclohexane                                  1,7-Diphenyl-4-heptanone                                                                      N-(3-aminopropyl)-N'-2-                                                                        N-[3-(1,7-diphenyl-4-heptylamino)propyl]-                    hydroxyethyl-1,4-cyclo-                                                                        N'-(2-hydroxyethyl)-1,4-cyclohexanebis-                      hexanebis(methylamine)                                                                         (methylamine)                                1,7-Di-(4-ethylphenyl)-4-                                                                     N-(3-aminopropyl)-N'-2-                                                                        N-{3-[1,7-di-(4-ethylphenyl)-4-heptyl-       heptanone       hydroxyethyl-1,4-cyclo-                                                                        amino]propyl}-N'-(2-hydroxyethyl)-1,4-                       hexanebis(methylamine)                                                                         cyclohexanebis(methylamine)                  1,5-Di-(2-isopropylphenyl)-                                                                   N,N'-bis-N-(3-hydroxypropyl)-                                                                  N-(3-hydroxypropyl)-N'-]1,5-di-(2-iso-       3-pentanone     1,4-cyclohexanebis-                                                                            propylphenyl)-3-pentyl]-1,4-cyclohexane-                     (methylamine)    bis(methylamine)                             1,9-Di-(2-ethylphenyl)-5-                                                                     N,N'-bis-N-(3-hydroxypropyl)-                                                                  N-[1,9-di-(2-ethylphenyl)-5-nonyl]-N'-       nonanone        1,4-cyclohexanebis-                                                                            (3-hydroxypropyl)-1,4-cyclohexanebis-                        (methylamine)    (methylamine)                                1-(3-Methylphenyl)-5-(4-                                                                      N-(3-aminopropyl)-N'-2-                                                                        N-(2-hydroxyethyl)-N'-{3-[1-(3-methyl-       n-butylphenyl)-4-pentanone                                                                    hydroxyethyl)-1,4-cyclo-                                                                       phenyl)-5-(4-n-butylphenyl)-4-pentylamino                                     ]-                                                           hexanebis(methylamine)                                                                         propyl}-1,4-cyclohexanebis(methylamine)      1,4-Di-(4-isopropylphenyl)-                                                                   N-(3-aminopropyl)-N'  -2-                                                                      N-(2-hydroxyethyl)-N'-{3-[1,4-di-(4-iso-     2-butanone      hydroxyethyl)-1,4-cyclo-                                                                       propylphenyl)-2-butylamino]propyl}-1,4-                      hexanebis(methylamine)                                                                         cyclohexanebis(methylamine)                  1-Phenyl-3-(4-t-butyl-                                                                        N-(2,3-dihydroxypropyl)-                                                                       N-(2,3-dihydroxypropyl)-N'-]1-phenyl-3-      phenyl)acetone  1,4-cyclohexanebis-                                                                            4-t-butylphenyl)-2-propyl]-1,4-cyclohexan                                     e-                                                           (methylamine)    bis(methylamine)                             1-(3,4-Dimethylphenyl)-5-                                                                     N-(2,3-dihydroxypropyl)-                                                                       N-(2,3-dihydroxypropyl)-N'-[1-(3,4-di-       (4-isopropylphenyl)-3-                                                                        1,4-cyclohexanebis-                                                                            methylphenyl)-5-(4-isopropylphenyl)-3-       pentanone       (methylamine)    pentyl]-1,4-cyclohexanebis(methylamine)      2,6-Diphenyl-4-heptanone                                                                      N-(2,3-dihydroxypropyl)-                                                                       N-(2,3-dihydroxypropyl)-N'-(2,6-diphenyl-                    1,4-cyclohexanebis-                                                                            4-heptyl)-1,4-cyclohexanebis(methylamine)                    (methylamine)                                                 1,7-Di-(4-t-butylphenyl)-                                                                     N-(3-aminopropyl)-1,4-                                                                         N-3-aminopropyl-N'-[1,7-di-(4-t-butyl-       4-heptanone     cyclohexanebis(methyl-                                                                         phenyl)-4-heptyl]-1,4-cyclohexanebis-                        amine)           (methylamine)                                                                 and                                                                           N-[4-(aminomethyl)cyclohexylmethyl]-N'-                                       [1,7-di-(4-t-butylphenyl)-4-heptyl]-1,3-                                      diaminopropane                               1,5-Di-(4-isopropylphenyl)-                                                                   N-(2-aminoethyl)-1,4-bis-                                                                      N-(2-aminoethyl)-N'-[1,5-di-(4-isopropyl-    3-pentanone     (2-aminoethyl)cyclohexane                                                                      phenyl)-3-pentyl]-1,4-bis-(2-aminoethyl)-                                     cyclohexane                                                                   and                                                                           N-[2-(4- 2-aminoethyl cyclohexyl)ethyl]-N                                     '-                                                                            [1,5-di-(4-isopropylphenyl)-3-pentyl]-                                        ethylenediamine                              1-(4-t-Butylphenyl)-6-(4-                                                                     N-(2-hydroxyethyl)-1,4-                                                                        N-(2-hydroxyethyl)-N' -[1-(4-t-butylpheny                                     l)-                                          i-propylphenyl)-3-hexanone                                                                    cyclohexanebis(methylamine)                                                                    6-(4-i-propylphenyl)-3-hexyl]-1,4-cyclo-                                      hexanebis(methylamine)                       1,7-Di-(4-ethylphenyl)-                                                                       N,N'-bis-(3-hydroxypropyl)-                                                                    N,N-bis-(3-hydroxypropyl)-N'-[1,7-di-(4-     4-heptanone     1,4-cyclohexanebis-                                                                            ethylphenyl)-4-heptyl]-1,4-cyclohexanebis                                     -                                                                             (methylamine)                                1-(4-i-propylphenyl)-3-                                                                       N-(2,3-dihydroxypropyl)-                                                                       N-(2,3-dihydroxypropyl)-N'-[1-(4-i-propyl                                     -                                            (3,4,5-trimethylphenyl)-                                                                      1,4-cyclohexanebis-                                                                            phenyl)-3-(3,4,5-trimethylphenyl)-2-propy                                     l]-                                          acetone         (methylamine)    1,4-cyclohexanebis(methylamine)              1,7-Di-(5-t-butyl-2-                                                                          N-(3-aminopropyl)-N'-(2-                                                                       N-(3-aminopropyl)-N-(2-hydroxyethyl)-N'-[                                     1,7-                                         methylphenyl)-4-heptanone                                                                     hydroxyethyl)-1,4-cyclo-                                                                       di-(5-t-butyl-2-methylphenyl)-4-heptyl]-1                                     ,4-                                                          hexanebis(methylamine)                                                                         cyclohexanebis(methylamine)                                                   and                                                                           N-[4-(aminomethyl)cyclohexylmethyl]-N-(2-                                     hydroxyethyl)-N'-[1,7-di-(5-t-butyl-2-                                        methylphenyl)-4-heptyl]-1,3-diaminopropan                                     e                                            1,5-Di-(4-isopropylphenyl)-                                                                   N-(3-aminopropyl)-1,4-cyclo-                                                                   N-(3-aminopropyl)-N'-[1,5-di-(4-             3-pentanone     hexanebis(methylamine)                                                                         isopropylphenyl)-3-pentyl]-1,4-cyclo-                                         hexanebis(methylamine)                                                        and                                                                           N-[4-(aminomethyl)cyclohexylmethyl]-N-                                        (3-aminopropyl)-N'-[1,5-di-(4-isopropyl-                                      phenyl)-3-pentyl]-1,3-diaminopropane         1,7-Di-(5-t-butyl-2-methyl-                                                                   N,N'-bis-(3-aminopropyl)-                                                                      N-(3-aminopropyl)-N'-[N-(1,7-di-(5-t-        phenyl)-4-heptanone                                                                           1,4-cyclohexanebis-                                                                            butyl-2-methylphenyl)-4-heptyl)-3-amino-                     (methylamine)    propyl]-1,4-cyclohexanebis(methylamine)      1,7-Di-(4-t-butylphenyl)-                                                                     N-(3-aminopropyl)-1,4-                                                                         N-3-aminopropyl-N'-[1,7-di-(4-t-butylphen                                     yl)-                                         4-heptanone     cyclohexanebis-  4-heptyl]-1,4-cyclohexanebis(methylamine)                    (methylamine)                                                                                  and                                                                           N-[4-(aminoethyl)cyclohexylmethyl]-N'-                                        [1,7-di-(4-t-butylphenyl)-4-heptyl]-1,3-                                      diaminopropane                               1,7-Di-(4-ethylphenyl)-                                                                       N,N'-bis-(3-amino-2-                                                                           N-(3-Amino-2-hydroxypropyl)-N'-{                                              3-[1,7-di-                                   4-heptanone     hydroxypropyl)-1,4-                                                                            (4-ethylphenyl)-4-heptylamino]-2-hydroxy-                    cyclohexanebis-  propyl}-1,4-cyclohexanebis(methylamine)                      (methylamine)                                                 1-(4-i-propylphenyl)-3-                                                                       N,N'-bis-(3-aminopropyl)-                                                                      N-(3-aminopropyl)-N'-3-[1-(4-i-propyl-       (3,4,5-trimethylphenyl)-                                                                      1,4-bis-(2-aminoethyl)-                                                                        phenyl)-3-(3,4,5-trimethylphenyl)-2-         acetone         cyclohexane      propylamino]propyl-1,4-bis-(2-amino-                                          ethyl)cyclohexane                            __________________________________________________________________________

EXAMPLE 2

Preparation ofN-(2-hydroxyethyl)-N'-[1-(4-isopropylphenyl)-4-phenyl-2-butyl]cyclohexylene-1,4-bis-(2-ethylamine)dichydrochloride.A mixture of 1-(4-isopropylphenyl)-4-phenylbutanone-2 (5.3 g., 0.02mole) and N-(2-hydroxyethyl)cyclohexylene-1,4-bis-(2-ethylamine) (21.4g., 0.1 mole) in 150 ml. of toluene is heated at reflux overnight with aDean-Stark spearator. The toluene is then removed under vacuum. Theresidual oil dissolved in 25 ml. isopropanol is added dropwise to sodiumborohydride (1.90g., 0.05 mole, excess) suspended in 50 ml. isopropanol.After complete addition, the reaction mixture is heated at reflux forone hour. The isopropanol is evaporated under reduced pressure, theresidue treated with water and the aqueous mixture extracted well withether. The combined ether extracts are back-washed with water, asaturated sodium chloride solution, dried over anhydrous sodium sulfateand concentrated under vacuum to leave the polyamine product.

This product is dissolved in ether and the solution cooled in anice-water bath. Hydrogen chloride gas is bubbled into the solution untilno further precipitate is formed. The solid is collected by filtration,washed with a small amount of ether, and dried under vacuum to leave thepolyamine dihydrochloride as a colorless product.

EXAMPLE 3

Preparation ofN-(3-aminopropyl)-N'-[1,7-di(2-methyl-5-t-butylphenyl)-4-heptyl]-1,4-bis-(2-aminoethyl)-cyclohexane.A mixture of 1,7-di-(2-methyl-5-t-butylphenyl)-4-heptanone (12.2 g.,0.03 mole) and 1,4-bis-(2-aminoethyl)cyclohexane (17 g., 0.1 mole) in250 ml. ethanol is heated at reflux overnight under vacuum. The cooledreaction mixture is hydrogenated with PtO₂ at room temperature and 40psi hydrogen pressure. The platinum catalyst is filtered off and theethanol removed under reduced pressure. The residual oil is dissolved inether and the ether solution washed several times with water to removethe excess diaminoethane.

The ether extracts are dried over anhydrous sodium sulfate andconcentrated under vacuum to leave an oil.

The oil is dissolved in 20 ml. tert-butanol and chilled to 0° C.-5° C.in an ice-water bath. Acrylonitrile (1.75 g., 2.2 ml., 0.033 mole) isadded dropwise over a 5-minute period. The reaction mixture is allowedto warm up to room temperature and is then heated at 60° C. overnight.The t-butanol was removed under reduced pressure. The residual oil wasdissolved in 150 ml. glacial acetic acid and hydrogenated with PtO₂ atroom temperature and 40 psi hydrogen pressure. The platinum catalyst isfiltered off and the acetic acid removed under vacuum. The residue isdissolved in ether and made basic with 10% sodium hydroxide. The ethersolution is washed with water, dried over anhydrous sodium sulfate andconcentrated under reduced pressure.

In addition to the compounds specifically set forth in the foregoingexamples, each of the respective ketones set forth in Preparations A andB when reacted with the individual amines set forth in the foregoingspecification especially at pahges 10 and 11 according to the method setforth in Example I produce the entire range of compounds describedaccording to this invention as embodied in Formula I.

What is claimed is:
 1. A compound of the formula: ##STR12## where R ishydrogen or loweralkyl; each n is alike or different and is the integer0 or 1;each R₁ is alike or different and is C₁ to C₄ alkylene; and Z is##STR13## where R₂ is 2-hydroxy-1,3-trimethylene, or R₁ as previouslydefined; R₃ is 2-hydroxy-1,3-trimethylene, or R₁ as previously defined;R₄ is hydrogen, aminoethyl, aminopropyl, C₁ to C₄ hydroxyalkyl,aminohydroxy C₂ to C₄ alkyl, or C₂ to C₄ dihydroxyalkyl; R₅ is hydrogen,C₁ to C₄ hydroxyalkyl or C₂ to C₄ dihydroxyalkyl, aminohydroxy C₂ to C₄alkyl, and n is as previously defined.
 2. A compound according to claim1 where n is
 3. A compound according to claim 2 where R₁ is methylene.4. A compound according to claim 2 where R₁ is ethylene.
 5. A compoundaccording to claim 2 where R₁ is trimethylene.
 6. A compound accordingto claim 1 where where A is 4-isopropylphenyl.
 7. A compound accordingto claim 1 where each A is 4-t-butylphenyl.
 8. A compound according toclaim 1 where each A is 2-methyl-5-t-butylphenyl.
 9. A compoundaccording to claim 1 where each A is 2,4,6-trimethylphenyl. 10.N-(3-Aminopropyl)-N'-[1,5-di-(4-isopropylphenyl)-3-pentyl]-1,4-bis-(2-aminoethyl)cyclohexane.11.N-[1,3-di-(4-t-butylphenyl)-2-propyl]-1,4-cyclohexanebis(methylamine).12.N-[1,7-di-(4-t-butylphenyl)-4-heptyl]-1,4-cyclohexanebis(methylamine).13.N-(3-Aminopropyl)-N'-[1,7-di-(4-isopropylphenyl)-3-pentyl]-1,4-bis-(2-aminoethyl)cyclohexane.14.N-(3-Aminopropyl)-N'-[1,5-di-(4-isopropylphenyl)-3-pentyl]-1,4-bis-(2-aminoethyl)cyclohexane.